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Antimicrobial effect of copper on multidrug-resistant bacteria

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Abstract

Copper has been used for centuries as a therapeutic agent in various cultures around the globe. With the emergence and spread of antibiotic resistance, the use of metallic copper alloys to control pathogenic microorganisms is attracting increasing attention. The antimicrobial effects of copper surfaces have been repeatedly demonstrated in both laboratory studies and clinical trials and copper surfaces have been attributed with great potential to limit the transmission and spread of pathogenic microbes. We investigated the antimicrobial effect of copper on three multidrug-resistant bacterial strains: methicillin-resistant Staphylococcus aureus sequence type 398, CTX-M-15 producing Escherichia coli and NDM-1 producing Klebsiella pneumoniae. Copper coupons were inoculated with bacterial cell suspensions and incubated at room temperature. At set time points, bacteria were resuspended and plated onto nutrient agar and colony-forming units were counted. Results show a more than fivefold log-reduction of viable bacteria for CTX-M-15 producing E. coli and NDM-1 producing K. pneumoniae after 60 min of incubation on metallic copper compared to stainless steel. The same reduction of viable bacteria could be demonstrated for methicillin-resistant S. aureus sequence type 398 after 120 min of incubation. Our data complement scientific evidence for copper's antimicrobial properties on multidrug-resistant bacteria and suggest that the use of copper surfaces constitutes an approach to support the control of these organisms.

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... Multiple resistant Enterobacteriaceae family had been responsible of many different infections e.g. urinary tract infections and blood stream infections, etc [15].Antibiotic resistance genes are found on chromosomes, plasmids, transposon and integrons. Transfer of antibiotic resistance plasmids could happened by different ways between same genera of bacteria horizontally and other time other genera vertically [18]. ...
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... Multiple resistant Enterobacteriaceae family had been responsible of many different infections e.g. urinary tract infections and blood stream infections, etc [15].Antibiotic resistance genes are found on chromosomes, plasmids, transposon and integrons. Transfer of antibiotic resistance plasmids could happened by different ways between same genera of bacteria horizontally and other time other genera vertically [18]. ...
Article
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... Steindl et al. carried out a study which tested antimicrobial effect of copper on multidrug-resistant bacteria, including Gram-negative bacilli such New Delhi metallo-beta-lactamase-1 (NDM-1) producing K. pneumoniae and extended spectrum β-lactamase (ESBL)-type cefotaxime-resistant-Munich (CTX-M) producing E. coli [14]. They have found complete reduction of the initial bacterial suspension density from around 1.5 × 10 8 after 60 min for NDM-1 K. pneumoniae and after 2 h for ESBL CTX-M E. coli. ...
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... The term multi-drug resistance (MDR) is used to describe bacteria that are able to resist one or more antibiotics in three or more antibiotic classes, while bacterial strains that are resistant to all antibiotics are termed as extreme drug resistant strains (Bassetti et al., 2013). Multidrug resistant Enterobacteriaceae have become an important cause of urinary tract and blood stream infections within the community setting (Steindl et al., 2012). Pseudomonas aeruginosa is a major nosocomial pathogen worldwide, intrinsically resistant to many drugs. ...
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... During this study, other methods of antimicrobial treatment will be explored, specifically in reference to copper as an alternative. With the emergence and spread of antibiotic resistance, the use of metallic copper alloys to control pathogenic microorganisms is attracting increasing attention (Steindl et al. 2012) Copper antimicrobial properties have been known for centuries even before germ theory. ...
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... ROS (Reactive Oxygen Species) express associated with cell die for different sizes of Cu NPs exposed these features could change through free surface energy of the particles directly associated to size and morphology and the pH inner of cells too [104]. The antimicrobial effect is directly related to the nanoparticle size and minimum inhibitory concentration (MIC) ( Table 4) and the oxidation degree of the surface [105]. ...
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Nano-sized metal particles show specific physical and chemical properties that allow the creation of new composites materials, which are important for multiple applications in biology and medicine such as infections control. Metal nanoparticles, mainly copper, exhibit excellent inhibitory effect in Gram-positive and Gram-negative bacteria; therefore the exploration about the efficient, economical and friendly environmental technics to synthesize inorganic nanoparticles is imperative. In this work a brief ov erview of the several methods is made including the comparison of the methods, mainly between sonochemical, microwave and chemical routes. It allows determining the optimal parameters and technical conditions to synthesize copper nanoparticles with physical and chemical properties suitable for the oral bacterial inhibition.
... Noyce et al. investigated copper's antimicrobial effects on different strains of MRSA and reported the complete killing of 10 7 cfu inoculums of MRSA (NTCT 10442) on copper [140]. Steindl et al. also reported that MRSA ST398, NDM-1-producing K. pneumonia and CTX-Mproducing E. coli were sensitive to copper, with less than 10 3 cfu remaining after 2 h [141]. Copper also exerts strong antibacterial effects through the bacterial intracellular influx of copper ions in the B. cepacia complex [136]. ...
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Bacteraemia caused by Enterobacteriaceae (EB) producing extended-spectrum β-lactamase (ESBL+) has been associated with higher mortality compared with non-ESBL-producing (ESBL-) EB bacteraemia in observational studies. We conducted a systematic review and meta-analysis of these studies to assess how adjusting for confounding in multivariate analyses affects the pooled estimate, and whether multivariate analyses that include intermediates in the causal pathway of outcome (sepsis severity and inadequate empirical therapy) have lower estimates of attributable mortality. PubMed search on 23 November 2010 followed by manually searching reference lists of included studies. Cohort studies published in English with separate mortality rates for ESBL+ and ESBL- EB bacteraemia. SYNTHESIS METHODS: Random-effects pooling of unadjusted and adjusted ORs followed by subgroup analyses to explore effects of adjustment procedures on adjusted ORs. The pooled OR for the unadjusted mortality associated with ESBL production was 2.35 (95% CI 1.90-2.91, I(2) = 42%, 32 studies). The pooled adjusted OR was 1.52 (95% CI 1.15-2.01, I(2) = 32%, 15 studies). Adjustment for more intermediates was associated with decreasing ORs. The pooled OR for the analyses adjusting for inadequate empirical therapy was 1.37 (95% CI 1.04-1.82). ESBL production in EB bacteraemia is associated with a higher mortality compared with bacteraemia with ESBL- EB, although the estimate of this association is affected by adjustment procedures. Adjustment for inadequate empirical therapy leads to a reduction in ORs, indicating that higher mortality is likely to be mediated through this phenomenon.
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The environment may act as a reservoir for pathogens that cause healthcare-associated infections (HCAIs). Approaches to reducing environmental microbial contamination in addition to cleaning are thus worthy of consideration. Copper is well recognised as having antimicrobial activity but this property has not been applied to the clinical setting. We explored its use in a novel cross-over study on an acute medical ward. A toilet seat, set of tap handles and a ward entrance door push plate each containing copper were sampled for the presence of micro-organisms and compared to equivalent standard, non-copper-containing items on the same ward. Items were sampled once weekly for 10 weeks at 07:00 and 17:00. After five weeks, the copper-containing and non-copper-containing items were interchanged. The total aerobic microbial counts per cm(2) including the presence of 'indicator micro-organisms' were determined. Median numbers of microorganisms harboured by the copper-containing items were between 90% and 100% lower than their control equivalents at both 07:00 and 17:00. This reached statistical significance for each item with one exception. Based on the median total aerobic cfu counts from the study period, five out of ten control sample points and zero out of ten copper points failed proposed benchmark values of a total aerobic count of <5cfu/cm(2). All indicator micro-organisms were only isolated from control items with the exception of one item during one week. The use of copper-containing materials for surfaces in the hospital environment may therefore be a valuable adjunct for the prevention of HCAIs and requires further evaluation.
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A study was designed to characterize extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli isolates causing bacteremia over an 8-year period (2000 to 2007) in a large well-defined geographical region. Molecular characterization was done by using isoelectric focusing; PCR; and sequencing of the blaCTX-M-, blaTEM-, blaOXA-, blaSHV-, and plasmid-mediated quinolone resistance determinants. Genetic relatedness was determined by pulsed-field electrophoresis with XbaI and multilocus sequence typing. A total of 67 patients with incident bloodstream infections were identified, and the majority presented with community-acquired infections involving the urinary and biliary tracts. Of the 67 ESBL-producing E. coli isolates recovered, 60 (90%) were positive for blaCTX-M genes; 32 (48%) produced CTX-M-15, 25 (37%) produced CTX-M-14, 1 (2%) produced CTX-M-24, 1 (2%) produced CTX-M-2, and 1 (2%) produced CTX-M-3, while 2 (3%) produced TEM-52 and 5 (7%) produced SHV-2. Twenty-four (36%) isolates were positive for aac(6′)-Ib-cr. The majority of isolates were resistant to ciprofloxacin (60 [90%] isolates) and gentamicin (40 [60%] isolates). The occurrence of ESBL-producing isolates was stable during the first 5 years, but there was a substantial increase from 2005 to 2007, mostly due to clone ST131, which produces CTX-M-15 and CTX-M-14, in blood cultures submitted from the community. Our results illustrated that E. coli clone ST131, which coproduces CTX-M-15, OXA-1, TEM-1, and aac(6′)-Ib-cr, has emerged as an important cause of community-onset bacteremia caused by ESBL-producing E. coli isolates; and this is the first study to identify CTX-M-14 in E. coli clone ST131.
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The retention of bacteria on food contact surfaces increases the risk of cross-contamination of these microorganisms to food. The risk has been considered to be lowered when the surfaces are dry, partly because bacterial growth and survival would be reduced. However, some non-spore-forming bacteria might be able to withstand dry conditions on surfaces for an extensive period of time. In this study the survival of Salmonella enteritidis, Staphylococcus aureus and Campylobacter jejuni on stainless steel surfaces at different initial levels was determined at room temperature. The transfer rates of these pathogens from kitchen sponges to stainless steel surfaces and from these surfaces to foods were also investigated. Staph. aureus was recovered from the surfaces for at least 4 days when the contamination level was high (10 5 CFU/cm2) or moderate (103 CFU/cm 2). At low levels (10 CFU/cm2), the surviving numbers decreased below the detection limit (4 CFU/100 cm2) within 2 days. S. enteritidis was recovered from surfaces for at least 4 days at high contamination levels, but at moderate level, the numbers decreased to the detection limit within 24 h and at low level within 1 h. C. jejuni was the most susceptible to slow-air-drying on surfaces; at high contamination levels, the numbers decreased below the detection limit within 4 h. The test microorganisms were readily transmitted from the wet sponges to the stainless steel surfaces and from these surfaces to the cucumber and chicken fillet slices, with the transfer rates varied from 20% to 100%. This study has highlighted the fact that pathogens remain viable on dry stainless steel surfaces and present a contamination hazard for considerable periods of time, dependent on the contamination levels and type of pathogen. Systematic studies on the risks of pathogen transfer associated with surface cleaning using contaminated sponges provide quantitative data from which a model of risks assessment in domestic setting could lead.
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Food-producing animals are the primary reservoir of zoonotic pathogens, and the detection of extended spectrum beta-lactamase (ESBL) producers among Escherichia coli and Salmonella strains has increased in recent years. ESBLs are widely detected in various human medical institutions but they are not so frequently reported in the bacterial population circulating in animals. This could indicate that these enzymes are less prevalent in animals than in humans, but also that they have not been extensively sought. The increasing occurrence of ESBL producers in animals is highlighted and discussed in this review with respect to the circulation of these resistance traits also among human pathogens.
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The medical community relies on clinical expertise and published guidelines to assist physicians with choices in empirical therapy for system-based infectious syndromes, such as community-acquired pneumonia and urinary-tract infections (UTIs). From the late 1990s, multidrug-resistant Enterobacteriaceae (mostly Escherichia coli) that produce extended-spectrum beta lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of UTIs. Recent reports have also described ESBL-producing E coli as a cause of bloodstream infections associated with these community-onset UTIs. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae, although comparative clinical trials are scarce. Thus, more rapid diagnostic testing of ESBL-producing bacteria and the possible modification of guidelines for community-onset bacteraemia associated with UTIs are required.
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